The objective of the research proposed during the fellowship period is to understand the role of Translation Elongation Factor 1 (EF-1) in catalyzing the guanine nucleotide exchange reaction on the G-protein EF-1. The exchange of GDP for GTP is hypothesized to be the rate-limiting step of translation elongation and key to maintaining the active pool of EF-1-GTP for delivering aminoacyl-tRNA to the ribosome. In order to address EF-1 function, we will utilize the yeast Saccharomyces cerevisiae for a coordinated molecular genetic and biochemical analysis. Biochemical analysis of mutant alleles of EF-1 already demonstrated to effect cell growth, fidelity, and translation rate, will provide a better understanding for the essential role of this protein. In vivo and in vitro analysis of these alleles along with future mutations devised on the basis of the NMR structure from the homologous human protein (hEF-1 will provide a logical set of experiments to analyze the mechanism of EF-1 function. Furthermore, the most interesting alleles will be the basis for a genetic screen to identify factors that regulate or modulate EF-1 or translation elongation. Analysis of EF-1 serves as both a study of post-transcriptional regulation and a model for interactions between guanine nucleotide exchange factors and their corresponding G-protein.